What is Synthetic Biology?

Synthetic biology or SynBio is an approach to engineer biology (cell). It is the union of engineering and biology that aims to make biology simpler and efficient.

Synthetic Biologist design and construct novel artificial biological systems or redesign the natural biological systems to perform useful functions. For example, diagnose a disease, engineered microorganisms that can detect toxins in the environment. Other sustainable products including bio-based fuels & chemicals, and valuable drugs such as vaccine, antibody and more.

All living creature comprised a set of information that is responsible to decides the way to look and what to perform. These instructions are cipher (encoded) in every organism’s genetic codes – also called organism DNA. What Synthetic biologists can do is to alter these cell’s DNA so that it behaves per specification, and to do something useful.

Synthetic Biology Definition

According to Encyclopedia Britannica, synthetic biology can be defined as “a field of research in which the main objective is to create fully operational biological systems from the smallest constituent parts possible, including DNA, proteins, and other organic molecules.”

Synthetic Biology is a Computer Metaphor

SynBio is often described using a computer metaphor. Cells are considered as Processors, while DNA is taken as a programming language and Proteins are considered as hardware. This standardization, allows Synthetic Biologists to program cell just like a computer.

The cell as an electronic circuit. Source: Wiley.com

Synthetic Biology History

The concept of synthetic biology was established in the 1800s when a German chemist Friedrich Wohler succeeded in making the first synthetic compound ever. He did this so by synthesizing Urea, an organic compound from inorganic sources such as ammonium chloride and silver isocyanate.

This was a revolution, as it proved the world that living things, which are organic, can be created by inorganic sources. However, the term “synthetic biology first appeared in 1910 by a French biologist” Stéphane Leduc in his publication.

The mid-1970s and 1980s were the recombinant DNA technology and Genetic engineering revolution. It leads to novel compounds, and one such example is synthetic insulin. It was during this time, Arber, Nathans, and Smith discovered restriction enzymes. This discovery helped synthetic biology in the early stages. Because of it, in 2000, two groups of researchers separately synthesized synthetic biological circuits and therefore laying down the foundations of synthetic biology.

The first-ever international conference on “synthetic biology 1.0” was held in Massachusetts Institute of Technology (MIT), Boston, on June 2004. The aims were to bring together synthetic biologists for the first time.

Synthetic Biology is an Interdisciplinary Approach

The most exciting aspects of synthetic biology are to integrate and coordinate beauty form each science field, including computer science, engineering, chemistry and of course Biology. It has gone elegantly into all possible fields of research.

Synthetic Biology integrates beauty from each possible science field.

Most of the researchers confuse synthetic biology with genetic engineering, biotechnology, and systems biology, even though they all share a common feature and this connected all these.

How Is Synthetic Biology different from Biotechnology?

Even though synthetic biology shares some common features with Biotechnology like both are concerned with producing different products, utilizing biology. But the core difference between them is that biotechnology alters or uses already present biological components. While synthetic biology does not entirely rely on the manipulation of those biological entities that only naturally occurs. But it also focuses more on synthesizing these biological things from scratches.

Synthetic biology focuses on ground-up approach, where you start from nothing and move upwards. The main idea behind biotechnology was that as we were already manipulating organisms, to give us our desired products by using techniques like genetic engineering and Recombinant DNA technology.

However, if we instead of manipulating, which comes with a considerable amount of risks. What if we engineer & synthesize them? Later these new synthetic organisms would act as factories and giving us our desired bioproducts, quickly and efficiently.

What is the main difference between synthetic biology and systems biology?

Similarly, synthetic biology focuses on synthesis. While systems biology focuses on the study of a specific biological component and its effects on its surroundings. Systems biology is a computational and mathematical modeling-based field. It uses a holistic approach for studying the interaction of various biological entities and phenomena.

Technologies empowering Synthetic Biology

Two main technologies paved the ways for synthetic biology, including

Artificial DNA Synthesis

The ability to rewrite or artificially produce DNA has allowed scientists and engineers to incorporate Processing, Manipulation, Fabrication, and Enhancement in biological systems.

Genome sequencing

On the other hand, genome sequencing is also helping synthetic biology to grow. The first genome sequencing took almost 13 years and billions of USD. Now you can sequence the whole genome within a couple of days. Also, entire DNA content and a total number of genes of an individual with a cost of 1000-3000 USD.

The cost of both DNA synthesis and sequencing are dramatically dropping over the past couple of years.

Synthetic Biology Goals

• The main idea of synbio is to utilize living organisms and use them as factories. Modifying and redesigning already present proteins and drugs, for enhancing efficacy. Also, artificial production of those compounds or materials, which source is a living being or processes. And that maybe have a massive risk in the negatively impacting environment and the lives of others involved in them.

Similarly using synthetic biological circuits to produce certain vital drugs efficiently and at a low cost.

• Biological Parts Standardization – to identify, design, construct and to make a catalog of standardized genomics/gene parts, i.e., Promoter, Ribosomal binding sites, open reading frame (ORF), and terminator. So, in the future, these standardized parts could be used efficiently and quickly to construct novel biological circuits and systems.

• To synthesize unnatural base pairs to expand the natural genetic code. Consequently, to make novel proteins that have not previously existed. Example include; in 2014 Dr. Floyd Romesberg from Scripps Research Institute create two unnatural base pairs, so-called X and Y. They aim to produce novel proteins that have some therapeutic uses.

Some Synthetic Biology Breakthroughs

In the 1970s, Her Gobind Khorana and his teammates made the first synthetic gene, outside a living system. The gene was from yeast, and it coded for tRNA (transfer RNA). While synthesis of the first protein-coding gene was successfully done in the laboratories of Herbert Boyer and Alexander Markham. However, these processes were not very profitable, because they were very time to consume, slow and prone to errors.

Today, gene synthesis is being carried out on a commercial scale. Companies like twist biosciences, integrated DNA technologies, Invitrogen and more provide their services for artificial gene synthesis. But this artificial gene synthesis was nowhere close to a fully synthesize genome.

In 2010, a scientist and entrepreneur, Craig Venter and his team, successfully created the first entire synthetic genome. This genome was formed by joining together long pieces of DNA made in the laboratory. While a bacterium, ‘’ Mycoplasma mycoides” was used as a reference genome, because it has one of the smallest genomes. Then they transplanted it into another bacterium, whose genome they had taken out. This was the first ever full synthetic genome created.

Craig Venter was not the only person to shine on the horizon of synthetic biology. Also, other giants stand beside him, taking synthetic biology to new frontiers. Some of these giants and their contribution to the development and growth of synthetic biology are:

Synthetic biology would not be what it was today if it was not for CRISPR. A new and powerful gene-editing tool allows researchers to very precisely edit the genome of almost any organism. It was the hard work of Jennifer Doudna and Emmanuelle Charpentier, who studied and used CRISPR in prokaryotes and showed its editing capabilities.

Later Feng Zhang used CRISPR for the first time on eukaryotes. He showed the potential of it in biotechnology, genetic engineering, and Synthetic biology.

Tom Knight, Drew Endy, Randy Rettberg, Gerald Jay Sussman, and their associates, developed the concept of standardizing synthetic biology and its components. They did so by introducing the bio-bricks concept, just like actual bricks join together to make a building. Similarly, these biobricks, worked together, by joining in specific ways, to create synthetic biological circuits.

These circuits are then integrated into organisms, e.g., a bacterium. Then this bacterium utilized that synthetic biological circuit to carry a specific function. The synthetic genetic circuit is just like an electronic circuit.

Biobricks are often conceptualized with the ‘legos’. Just like different ‘legos’ combine to build something big and unique. Similarly, different biobricks combine to build larger biological components including DNA fragments, gene, and even whole genome.

The biobricks are different DNA sequence and pieces, which are standard and the same throughout the world. These include transcription start sites, ribosomal binding sites, coding regions, start and stop codons. Another good thing about biobricks is that anyone can register a sequence or anyone can make a biobrick and can store in a database known as Registry of Standard Biological Parts.

Jay keasling, another synthetic biologist, who succeeded in synthesizing synthetic artemisinin. A drug that is highly potent against malaria. Being synthetic makes it easier in batch production and makes the whole process fast and environmentally friendly.

George Church is considered as the father of synthetic biology. From finding out the functions of introns in regulations and further modifying and making the work of CRISPR better in gene therapies. Also, to multiplex genome sequencing, a type of genome sequencing in which different DNA molecules are sequenced at the same time, using specific tags or dyes of each type.

Dr. Church also paved the way for next-generation sequencing. Sequencing which once took almost 13 years, now due to next-generation sequencing takes only a couple of days. He also developed a technique known as DNA chip, in which multiple DNA samples can be screened, checked and sequenced.

Thus, making synthetic biology very fast, cheap and efficient. Recently, he was successful in inserting genes of a mammoth in an elephant, maybe making it possible for bringing extinct organisms back to life one day.

Some Synthetic Biology Applications

The beauty of synthetic biology is that its applications range from making compounds like alcohols or drugs, biofuels, to whole organisms on a large scale. In the case of biofuels, microorganisms are utilized to produce fuels based on solar energies and by generating energy by decomposing waste materials.

Similarly, work on industrial enzymes is being carried out, so that they can degrade those materials and compounds, which were either non-degradable or would deteriorate very slowly, like oil and plastic waste.

Bio-based chemicals and products are getting hold also, in which chemicals or products are extracted from synthetic organisms. Instead of utilizing their traditional sources, making it more environmentally friendly, more comfortable, and cheaper.

Applications of Synthetic Biology. Source: Synbiobeta

Synbio also focuses on the better production of vaccines and antibodies, to overcome the problems of antibiotic resistance, which is currently a grave concern.

Sometimes traditional ways of detecting and checking the quality of water or air, or some other source for contamination is not effective. For these biosensors are being made. These are modified organism, which will glow or will report the presence of specific contaminants after reacting with them. Similarly, bio-filters being created used not only for detection but also for removing the pollutants.

As an alternative to chemotherapy and radiotherapy, which usually have many harmful effects, synthetically modified cancer-killing viruses are created. A researcher from MIT, Timothy Lu, has shown this in animal model studies, that when viruses loaded with synthetic biological circuits for specific molecules, like signaling molecules, can successfully battle cancerous tumors and cells.

Example of Synthetic Biology Companies

Apart from these scientists, there are also certain companies that have found their fortune in synthetic biology. They are working in the developing of synbio, in various ways;

Twist Bioscience

DNA synthesizing company founded by Emily Leproust & Bill Peck in 2013. Their primary goal is to synthesize synthetic DNA, parts of DNA and genes. The company goes public in 2018, sold 5 million shares with each $14. Also, on their debut in Stock Market, the company raised $70 million.

Ginkgo Bioworks

Co-founded by Tom Knight and his MIT colleagues in 2009. Gingko works on the organism level. They synthesize synthetic organisms for various useful purposes, like fuel producing yeasts, or oil or plastic degrading bacteria and more. In 2018, the company went with Bayer (pharmaceutics giant) and established a joint venture “Joyn Bio” aims to enhance the nitrogen fixation capabilities of soil bacteria for Plants.

Autolus

Autolus, since its inception in 2014, is working on Cancer Therapies, by synthesizing novel T-cells, which then recognizes cancerous cells and destroy them.

Precision Biosciences

A genome editing company is working on curing genetic diseases by editing the genomes of the affected individuals.

Also, CRISPR Therapeutics, co-founded by Jennifer Doudna and her colleagues to utilized the potential of CRISPR to treat some severe diseases.

Gevo

Based in Englewood, Gevo is focused on advanced renewable chemicals and next-generation biofuels.

Impossible Foods

The company is working in the field of food and nutrition. Just as its name implies, they are working on producing and making food from unconventional sources, like producing meat, from non-animal sources by culturing cells in the lab. Billionaire giants like Bill Gates and Richard Branson bet on this company.

More synthetic biology companies working on lab-grown meats include; Memphis Meats, Mosa Meats, and Beyond Meats. These startups aim to resolve environmental issues by making sustainable foods in the lab. Also, to stop the slaughtering of animals by preventing the diseases transferring from animals to humans.

Ethical Concern of Synthetic Biology

Synthetic biology with such huge potential also comes with very serious risks and dangers. There are now increasing chances of high-level bio-terrorism. And even possibilities of natural disasters, in case of synthetic organisms escapes into the environment either intentionally or unintentionally.

Therefore, there are ethical concerns regarding the misuse of these technologies. However, on the positive note, synthetic biology is not that much of a threat. Because there are fields like genetic engineering and recombinant DNA technology, before synbio and none of them have ever attempted to work with such things.

Even though DNA sequencing is cheaper than ever, but still DNA synthesis is still an expensive process, and it is not affordable for everyone.

Get involved in Synthetic Biology

The unique thing that separates synthetic biology from other fields is that in this field networking is easily done. People from every walk of life and come and join it. For example, DIYbio which was founded in 2008, is a community of people from different fields, who come together and work on do-it-yourself bio-projects. This encourages everyone to join and interact with one another.

Another such network is Synbiobeta, where engineers, scientists, investors and people having a passion for biology and science comes together to solve different problems that we are facing nowadays.

While competitions like iGEM (international genetically engineered machines) and BioMod (bimolecular design competition), in which students compete against one another, on a global level.